EGFR突变对肺腺癌预后及治疗意义生物信息分析

SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION IN THE PROGNOSIS AND TREATMENT OF LUNG ADENOCARCINOMA:A BIOINFORMATICS ANALYSIS

目的探讨表皮生长因子受体(EGFR)突变对肺腺癌预后及治疗的意义。方法从癌症基因组图谱(TCGA)数据库下载肺腺癌的RNA测序数据、基因表达矩阵及临床信息,应用基因突变景观分析了解EGFR在肺腺癌中的突变情况,分析与EGFR突变相关的临床特征。利用差异分析得到差异表达基因(DEGs),基于DEGs的重叠基因构建LASSO-Cox风险预后模型,依据模型风险评分中位值将样本分为高、低风险组进行Kaplan-Meier生存分析。应用单因素Cox风险比例回归分析肺腺癌预后特征基因,并对其与EGFR突变相关性进行分析。分析EGFR突变与免疫细胞浸润和铁死亡基因的关系。结果EGFR在肺腺癌中的突变率为11.64%,EGFR突变与性别(χ^(2)=5.139,P<0.05)和吸烟(χ^(2)=36.822,P<0.01)有关。生存分析显示,高风险组生存率较低(HR=1.932,95%CI=1.433~2.606,P<0.05)。GLB1L3、TMEM63C、FAM83A基因与肺腺癌的预后相关,其中GLB1L3、TMEM63C与EGFR突变呈正相关(r=0.3831、0.3826,P<0.05)。肺腺癌组织中CD8^(+)T细胞比例较高,且与EGFR突变状态相关;在EGFR突变型和野生型肺腺癌中,有10个铁死亡基因表达差异具有统计学意义(t=1.896~3.765,P<0.05)。结论EGFR突变与肺腺癌的不良预后相关,且与肿瘤免疫细胞浸润和铁死亡存在紧密联系,这为肺腺癌的治疗提供了新思路。

Objective To investigate the significance of epidermal growth factor receptor(EGFR)mutation in the prognosis and treatment of lung adenocarcinoma.Methods RNA sequencing data,gene expression matrix,and clinical information of lung adenocarcinoma were downloaded from the Cancer Genome Atlas database,a gene mutation landscape analysis was used to investigate EGFR mutation in lung adenocarcinoma,and the clinical features associated with EGFR mutation were analyzed.A differential analysis was performed to obtain differentially expressed genes(DEGs),and a LASSO-Cox risk prognostic model was constructed based on the overlapping genes of DEGs.The samples were divided into high-and low-risk groups based on the median risk score of the model,and then the Kaplan-Meier method was used to perform the survival analysis.A univariate Cox proportio-nal-hazards regression model analysis was used to investigate the characteristic genes associated with the prognosis of lung adenocarcinoma,and their correlation with EGFR mutation was analyzed.The association of EGFR mutation with immune cell infiltration and ferroptosis genes was analyzed.Results The rate of EGFR mutation was 11.64%in lung adenocarcinoma,and EGFR mutation was associated with sex(χ^(2)=5.139,P<0.05)and smoking(χ^(2)=36.822,P<0.01).The high-risk group had a relatively low survival rate(HR=1.932,95%CI=1.433-2.606,P<0.05).The GLB1L3,TMEM63C,and FAM83A genes were associa-ted with the prognosis of lung adenocarcinoma,among which GLB1L3 and TMEM63C were positively correlated with EGFR mutation(r=0.3831,0.3826,P<0.05).There was a relatively high proportion of CD8^(+)T cells in lung adenocarcinoma tissue,which was correlated with the status of EGFR mutation,and there were significant differences in the expression of 10 ferroptosis genes between EGFR-mutant lung adenocarcinoma and wild-type lung adenocarcinoma(t=1.896-3.765,P<0.05).Conclusion EGFR mutation is associated with the poor prognosis of lung adenocarcinoma and is closely associated with tumor immune cell infiltration and ferroptosis,which provides new ideas for the treatment of lung adenocarcinoma.